Biofilms are mucilaginous communities of microorganisms such as bacteria, archaea, fungi, molds, algae or protozoa or mixtures thereof that grow on various surfaces (see Nature, vol. 408, pp. 284 286, Nov. 16, 2000). Biofilms form when microorganisms establish themselves on a surface and activate genes involved in producing a matrix that includes polysaccharides. The compositions of the present invention may prevent or retard biofilm formation by interfering with a microorganism's ability to attach to a surface.
Molecules called quorum-sensing signals help trigger and coordinate part of the process of forming a biofilm after the microorganism attaches to the surface. Bacteria constantly secrete low levels of the signals and sense them either through receptors on their surfaces, or internally. The receptors trigger behavioral changes when there are enough bacteria to allow the signals' concentrations to achieve a critical threshold. Once this occurs, bacteria respond by adopting communal behavior, such as forming a biofilm, and in the case of pathogenic bacteria, deploying virulence factors such as toxins. In addition to communicating with members of their own species, bacteria also conduct inter-species communications, such that a biofilm may contain more than one species of bacteria.
Biofilms develop preferentially on inert surfaces including those of everyday and household items. Biofilms may form on polymeric materials (e.g., thermoplastic and thermoset), woods, metals, glass and ceramics found in the home and in public areas. For example, biofilm formation is commonplace on sinks and countertops. Exposure to such microorganisms through skin-surface contact may result in infections that compromise the health of the public. In addition to sinks and countertops, biofilms may form on any number of items with which persons come into contact such as: floors, walls, shopping carts, toys, furniture, shelving, hygiene products, playground equipment, and so forth. Controlling formation of biofilms in these areas could result in less infection of individuals in the home and in public.
Biofilm formation has important public health implications as well. Drinking water systems are known to harbor biofilms, even though these environments often contain disinfectants. Any system providing an interface between a surface and a fluid has the potential for biofilm development. Water cooling towers for air conditioners are well-known to pose public health risks from biofilm formation, as episodic outbreaks of infections like Legionnaires' Disease attest. Turbulent fluid flow over the surface does not provide protection; biofilms can form in conduits where flowing water or other fluids pass, with the effects of altering flow characteristics and passing planktonic organisms downstream. Industrial fluid processing operations have experienced mechanical blockages, impedance of heat transfer processes, and biodeterioration of fluid-based industrial products, all attributable to biofilms. Biofilms have been identified in flow conduits like hemodialysis tubing, and in water distribution conduits. Biofilms have also been identified to cause biofouling in selected municipal water storage tanks, private wells and drip irrigation systems, unaffected by treatments with up to 200 ppm chlorine.
Biofilms are a constant problem in food processing environments. Food processing involves fluids, solid material and their combination. As an example, milk processing facilities provide fluid conduits and areas of fluid residence on surfaces. Cleansing milking and milk processing equipment presently utilizes interactions of mechanical, thermal and chemical processes in air-injected clean-in-place methods. Additionally, the milk product itself is treated with pasteurization. In cheese production, biofilms can lead to the production of calcium lactate crystals in cheddar cheese. Meat processing and packing facilities are in like manner susceptible to biofilm formation. Non-metallic and metallic surfaces can be affected. Biofilms in meat processing facilities have been detected on rubber “fingers,” plastic curtains, conveyor belt material, evisceration equipment and stainless steel surfaces. Controlling biofilms and microorganism contamination in food processing is hampered by the additional need that the agent used not affect the taste, texture or aesthetics of the product.
Microbial infection, and the subsequent formation of biofilms remains one of the most serious complications in several areas, particularly in medical devices, drugs, health care and hygienic applications, water purification systems, hospital and dental surgery equipment, textiles, food packaging and food storage (See Biomacromolecules, vol. 8 no. 5, pp. 1359-1384, May 2007). Since the difficulties associated with eliminating biofilm-based infections are well-recognized, a number of technologies have developed to treat surfaces or fluids bathing surfaces to prevent or impair biofilm formation. Biofilms adversely affect medical systems and other systems essential to public health such as water supplies and food production facilities. A number of technologies have been proposed that treat surfaces with organic or inorganic materials to interfere with biofilm development. For example, various methods have been employed to coat the surfaces of medical devices with antibiotics (See e.g. U.S. Pat. Nos. 4,107,121, 4,442,133, 4,895,566, 4,917,686, 5,013,306, 4,952,419, 5,853,745 and 5,902,283) and other bacteriostatic compounds (See e.g U.S. Pat. Nos. 4,605,564, 4,886,505, 5,019,096, 5,295,979, 5,328,954, 5,681,575, 5,753,251, 5,770,255, and 5,877,243). Additionally, significant advances in the last three decades have been made in the synthesis and application of polymers to prevent microbial attack and degradation in many contexts. (See Biotechnol. Bioact. Polym., pp. 225-237, 1994). Despite these advances, contamination of medical devices and invasive infection therefrom continues to be a problem.
Any agent used to impair biofilm formation that will be exposed to individuals must be safe to the user. Certain biocidal agents, in quantities sufficient to interfere with biofilms, also can damage host tissues. Thus, it is advantageous for the biofilm resistant compound to function not as a biocide, but to render surfaces unsuitable for adhesion and colonization by microoorganisms. Such a compound relies not on a “kill mechanism” for the prevention of biofilms, but on creating an environment not conducive to biofilm formation.
Until now, it has been postulated that smoother surfaces may delay the initial build up of microorganisms on a surface during biofilm formation, but will not significantly affect the amount of biofilm that will attach to the surface. (See “The key to understanding and controlling bacterial growth in Automated Drinking Water Systems, Second Edition” by Edstrom Indus., Inc., pg. 7, June 2003). The present invention demonstrates that biofilm formation may be prevented by coating a surface with the present invention or by incorporating the present invention into the substrate as a whole. The mechanism by which the present invention retards the formation and growth of biofilms is by creating a surface wherein microorganisms associated with biofilms do not adhere or colonize, in part due to the smoothness of the surface coated, or integrated, with the compositions and compounds of the present invention.